ClinicalTrials.gov record NCT02974595
Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This prospective observational study collects clinical, genetic, immunologic, and other laboratory data from people with various autoinflammatory diseases, unaffected blood relatives, and healthy adult volunteers. Participants give medical history, undergo physical exams, blood tests and other evaluations; imaging and questionnaires are common, and some may have procedures like lumbar puncture or skin biopsy if indicated. Visits can be in-person (multi-day) or virtual with mail-in samples, and participants may be followed for up to 15 years.
What it is studying. The study tests how autoinflammatory diseases develop and change over time by measuring clinical features, immune system patterns, genetic causes, metabolic/endocrine characteristics, and biomarkers during flares and quiescent periods. It also aims to document organ-specific outcomes and the long-term course of these conditions.
What the researchers hope to learn. Understand the underlying immune dysregulation and genetic causes of autoinflammatory diseases. Identify biomarkers that change with disease activity (flares versus quiescence). Characterize clinical, metabolic, and organ-specific outcomes over time. Build data and samples to inform future research and the development of possible new treatments.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
Background: Some diseases cause chronic inflammation with intermittent flares in the body. These are called autoinflammatory diseases. They can cause fevers, rashes, ulcers, and other problems. Researchers want to learn more about the causes and effects of these diseases. They hope this will improve how the disease is managed in the future. Objectives: To understand the underlying immune dysregulation To identify the genetic cause To translate our findings into novel treatments that improve patients disease outcomes Eligibility: Patients with known NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still's Disease, and with other yet undifferentiated autoinflammatory diseases. Unaffected relatives of participants with a known or undifferentiated autoinflammatory disease Healthy adult volunteers at least 18 years of age Design: Participants will be screened with blood sample and medical history. They may provide copies of their medical records. Enrolled participants will be evaluated at the NIH for 2-5 days. All participants will have a detailed medical history, physical exam, blood tests, and other evaluations depending on the extent of their autoinflammatory disease. Participants may also expect the following assessments:
- Clinical tests that help assess organ damage and function such as hearing, vision, memory, and learning tests.
- Imaging studies to characterize organ involvement of the inflammatory disease including: X-rays, CT scans, special MRIs, and bone scans.
- Laboratory evaluations including clinical markers of disease activity, research samples for genetic studies, blood samples for cytokine/biomarker assessment, and gene expression profiling.
- Questionnaires to assess disease activity and quality of life.
- If indicated, other procedures may be administered that include: a lumbar puncture if CNS inflammation is suspected, a skin biopsy if skin inflammation is present, and/or gastrointestinal and pulmonary procedures if they are clinically indicated.
Participants may return for a single follow-up visit or for long-term follow-up visits depending on their disease and willingness to return. Long-term follow-up may occur for up to 15 years on this protocol.
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- INCLUSION CRITERIA - AFFECTED PARTICIPANTS:
- Be 2 to 99 years old for participants who will be seen at the NIH CC; be 0 (newborn) to 99 years old for participants who participate remotely via a virtual protocol visit and will submit mail-in samples. Participants younger than 3 years will be seen in the outpatient clinic at the NIH CC if approved by the Pediatric
- Consult Service as per NIH CC policy and guidelines.
- Is willing to allow storage of biological specimens for future use in medical research.
- Is willing to allow genetic testing on collected biological samples.
- Has a primary care or other physician who will manage all health conditions related or unrelated to the study objectives.
- Fulfills one of the following criteria:
- Has a known disease-causing genetic mutation associated with NOMID/CAPS, DIRA, CANDLE, SAVI, or NLRC4-MAS.
- Has clinical signs or symptoms not explained by any other disorder (eg, infections, malignancies) and are consistent with a possible IL-1 mediated autoinflammatory disease. Participants must meet both of the following criteria:
- Clinical characteristics strongly consistent with an IL-1 mediated autoinflammatory disease per the following criteria and at the discretion of the principal investigator (PI). Individuals must have a past or present history of one of the following to be considered for study enrollment:
- Recurrent fever that has gone undiagnosed after reasonable attempts, and that is consistent with the conditions under study in this protocol
- Neutrophilic urticaria, pustular dermatitis, erysipelas-like erythema, or urticarial rash
- Epiphyseal and/or patella enlargement, periostitis, myalgias, arthralgias, arthritis, or recurrent multifocal aseptic osteomyelitis
- Sensorineural hearing loss
- Chronic aseptic meningitis or CNS vasculitis
- Conjunctivitis, episcleritis, uveitis, papilledema, pleuritis, pericarditis, aseptic peritonitis, early onset enterocolitis, hepatosplenomegaly, or lymphadenopathies
- Laboratory characteristics strongly consistent with an IL-1mediated autoinflammatory disease per the following criteria. Individuals must havepast or present history of evidence of systemic inflammation (eg, elevation of C-reactive protein [CRP] and/or erythrocyte sedimentation rate [ESR], anemia, thrombocytosis).
- Has clinical signs or symptoms not explained by any other disorder (eg, infections, malignancies) and are consistent with a possible IFN-mediated, autoinflammatory disease.1,36 Participants must meet both of the following criteria:
- Clinical characteristics strongly consistent with an IFN-mediated autoinflammatory disease per the following criteria and at the discretion of the PI. Individuals must have a past or present history of one of the following to be considered for study enrollment:
- Recurrent fevers that has gone undiagnosed after reasonable attempts, and that is consistent with the conditions under study in this protocol
- Panniculitis, ischemic ulcerative skin lesions, chilblain lesions, or livedo reticularis
- Lipodystrophy
- Myositis, arthralgias, arthritis, or joint contractures
- Basal ganglia calcifications or white matter CNS disease
- Interstitial lung disease, lung fibrosis, or pulmonary hypertension
- Conjunctivitis, episcleritis, cortical blindness, glaucoma, papilledema, or hepatosplenomegaly
- Laboratory characteristics strongly consistent with an IFN-mediated autoinflammatory disease per the following criteria. Individuals must have past or present history one or more of the following to be considered for study enrollment:
- Evidence of systemic inflammation (eg, ESR or CRP)
- Cytopenias (eg. leukopenia, anemia, or thrombocytopenia)
- Dyslipidemia or insulin resistance
- Abnormal liver function test, creatinine kinase (CK), or LDH
- Has clinical signs or symptoms consistent with an undifferentiated autoinflammatory disease (including but not limited to dysregulation in other proinflammatory cytokines such as IL-17, TNF, IL-18, and others). Participants must meet one of the following criteria:
- Clinical characteristics strongly consistent with an undifferentiated autoinflammatory disease. Individuals must have a past or present history of one of the clinical and one of the laboratory characteristics mentioned above to be considered for study enrollment.
- Individuals with defined organ inflammation associated with past or current evidence of systemic inflammation.
- Alternatively to #5, had been enrolled in the past as an affected participant on NIAMS study 03-AR-0173 and or had samples collected on 03-AR-0173.
- INCLUSION CRITERIA - UNAFFECTED RELATIVES OF AFFECTED PARTICIPANTS:
- Be 2 to 99 years old for participants who will be seen at the NIH CC; be 0 (newborn) to 99 years old for participants who participate remotely via a virtual protocol visit and will submit mail-in samples. Participants younger than 3 years will be seen in the outpatient clinic at the NIH CC if approved by the Pediatric Consult Service as per NIH CC policy and guidelines.)
- Be related by blood to an affected participant.
- Is willing to allow storage of biological samples for future use in medical research.
- Is willing to allow genetic testing on collected biological samples.
- Does not fulfill any of inclusion criterion #5 for affected participants.
- Is able to provide informed consent.
- INCLUSION CRITERIA - HEALTHY VOLUNTEERS:
- Be at least 18 years old.
- Not be related to an affected participant.
- s willing to allow storage of biological samples for future use in medical research.
- Is willing to allow genetic testing on collected biological samples.
- Does not fulfill any of inclusion criterion #5 for affected participants.
- Is able to provide informed consent.
- PARTICIPANT
Exclusion criteria
- Presence of conditions that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.
- Oncological evaluation suggestive of lymphoma, leukemia or multiple myeloma, except for participants with a known primary diagnosis of an autoinflammatory disease who subsequently developed a malignancy. These patients will not be excluded from the study.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
Autoinflammatory diseases are a group of immune dysregulatory diseases that are characterized by recurrent episodes of systemic as well as organ-specific inflammation that can involve the skin, eyes, joints, bones, muscles, lungs, serosal surfaces, inner ear, brain, and other organs. The prominent role of IL-1 in the pathogenesis of these disorders first became evident through the discovery of mutations in the gene NLRP3 and IL1RN. Since then, we have identified additional mutations that cause autoinflammatory diseases, including mutations in proteasome components and STING1 that suggest a role of increased type I IFN signaling as a contributor to the disease pathogenesis of autoinflammatory diseases and in NLRC4 and CDC42 that suggest a role of IL-18 in some autoinflammatory diseases. In this natural history study, we seek to comprehensively evaluate people with autoinflammatory diseases that include clinical, genetic, immunologic, andendocrinologic characterizations. Other rare diseases not mediated by IL-1, IL-18 or type I IFN and presumed to be autoinflammatory diseases with unknown genetic causes may also be eligible under this protocol. In addition, we intend to evaluate long-term outcomes and biomarkers over time in selected diseases. We plan to follow most participants for the duration of this study (15 years). Relatives who do not have autoinflammatory diseases as well as healthy volunteers will also be recruited to serve as controls for biomarker, genetic, and other molecular analyses.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
After screening with a blood sample and medical history (and possibly copies of medical records), participants undergo a 2–5 day evaluation visit or a remote visit with mail-in samples. Evaluations include a detailed history and exam, blood tests and research sample collection for genetic and biomarker studies, questionnaires, and tests to assess organ function (hearing, vision, memory). Participants may have imaging (X-ray, CT, special MRI, bone scan) and, if clinically indicated, procedures such as lumbar puncture, skin biopsy, or gastrointestinal or pulmonary procedures. Follow-up may be a single visit or long-term visits up to 15 years; biological samples will be stored for future research per participant agreement.
How the study is structured. A prospective observational cohort. People with defined or undifferentiated autoinflammatory diseases, their unaffected blood relatives, and healthy adults are enrolled as groups. After screening with medical history and blood samples, enrolled participants have detailed evaluations (multi-day in-person visits or virtual visits with mail-in samples) including exams, blood and other laboratory tests, imaging, questionnaires, and selective procedures when clinically indicated. Participants may return for one follow-up visit or for long-term follow-up for up to 15 years.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on cryopyrin-associated periodic syndromes
This trial is also listed on this site under familial Mediterranean fever.
Important dates
- Study start
- Dec 9, 2016
- Primary completion
- Aug 31, 2031 (estimated)
- Study completion
- Sep 30, 2032 (estimated)
- Target enrollment
- 3200 participants (estimated)
- Last updated on registry
- Sep 22, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Katsiaryna Uss 📞 (240) 292-4709 ✉ kat.uss@nih.gov
- Raphaela T Goldbach-Mansky, M.D. 📞 (301) 761-7553 ✉ goldbacr@mail.nih.gov
Participating sites (1)
- National Institutes of Health Clinical CenterRecruiting
Bethesda, Maryland, 20892 · United States
- For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) · 800-411-1222 ext. TTY8664111010 · prpl@cc.nih.gov
Terms used on this page · explanations by MedicalUpdates.ai
- CT
- An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.
- biomarker
- Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
- lumbar puncture
- A procedure in which a needle is placed between the bones of the lower back to collect spinal fluid or to give a treatment.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- long-term follow-up
- Observation that continues for years after the study treatment, often required for gene and cell therapies.
- INCLUSION CRITERIA
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- principal investigator
- The doctor or scientist responsible for running the study at a site or overall.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- EXCLUSION CRITERIA
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- natural history study
- A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials